Stimulation of bone formation with an in situ setting tricalcium phosphate/rhBMP‐2 composite in rats

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Abstract
The aim of the study was to determine bone-regenerative effects of an in situ setting tricalcium phosphate (TCP) cement combined with rhBMP-2 and to compare it with autologous bone graft. A trepanation defect of 1.5 mm in the femur diaphysis of Sprague–Dawley rats was filled with an in situ setting TCP cement combined with 0, 0.25, 2.5, or 25 μg of rhBMP-2, an autologous bone graft, or left empty. The rats were euthanized after 1 and 3 weeks and examined by radiography, histology, histomorphometry, and bending tests. All TCP groups with or without BMP-2 showed a good bony ingrowth with a close bone–cement contact. Histomorphometric analysis showed no increase of new bone formation in the defect, but a dose-dependent increase in callus formation with a maximum at 25 μg of rhBMP-2. As shown with intravital fluorochrome staining, new bone formation started earlier using rhBMP-2. Bone strength, measured in a three-point bending test and expressed in percentage of the contralateral healthy femur, was 75% for TCP + 25 μg rhBMP-2, 44% for TCP + 2.5 μg rhBMP-2, and 34% for autologous bone graft. TCP particles were detectable in all groups after 3 weeks. Callus formation and bending strength of the TCP + 25 μg rhBMP-2 group was superior to autologous bone graft. So TCP/rhBMP-2 composites may prove to be an effective substitute for autologous bone grafts. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 65A: 17–23, 2003